1. Field of the Invention
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The present invention relates to an anti-cancer composition containing acridine derivatives and guanosine compounds. In the composition of the present invention, the acridine derivative and the guanosine compound are present in the weight ratio of 1:0.1-5.0, preferably 1:0.3-3.0 and more preferably 1:0.5-1.5.
2. Background Art
A tumor is a disease in which cells are excessively proliferating for some reasons in the living body. Cancer is a malignant tumor which is thought as being the "progressive, uncontrolled and unlimited proliferation of cells". The uncontrolled proliferation means that cells can continuously proliferate by avoiding physiological surveillance and various suppressive factors in the living body, although some exceptions may be present. Cancerous cells are characterized by low serum requirement and active proliferation even in diluted blood. Cancer cells can produce growth factors which assist unregulated malignant proliferation.
Cancer or neoplasm is a cell population which carries excessive and self-regulating proliferation to invade the living body, and the malignant tumor tends to invade the healthy tissues resulting in infiltrating proliferation. In addition, the cancer cells may be shed and disseminated to other organs and tissues through blood or lymph node, resulting in the formation of the secondary cancer (i.e., metastasized cancer). Metastatic cancer in the human body is one of the most fatal diseases which produces an extremely high mortality and causes intolerable pain. Currently the incidence of cancer keeps increasing.
Advances in molecular and cellular biology of cancer have revealed that oncogenes and tumor suppressor genes are involved in the induction of neoplasms and that carcinogenesis is also associated with the intervention of signal transduction systems, which affect cell proliferation, genes and regulatory systems of gene expression, and the like. When oncogenes are activated, an increase in expression and cell division occurrs, whereas tumor suppressor genes are generally involved in suppression of cell division and proliferation. It is generally accepted that cancer cells with unlimited proliferation are expressed due to a certain abnormality of the proliferation stop mechanism which involves proliferative factors, proliferation inhibiting factors, intracellular substrates, cell surface molecules, and the like.
At present, it is well known that chemotherapeutic agents currently used for the treatment of malignant tumors have limitations in clinical applications due to their serious adverse effects such as bone marrow suppression and gastro-intestinal disturbances, and thus cannot sufficiently provide successful treatment of cancer. Furthermore, more potent cancer chemotherapeutic agents exhibit more serious toxicities, unpleasant feelings and intoxications, etc., besides the symptoms resulting from cancer itself. Currently, the treatment of cancer includes surgery, radiotherapy, chemotherapy, endocrinological therapy, immunological therapy, and the like. Anti-cancer agents being used for treatment of a malignant tumor may kill normal cells as well as cancerous cells. Because of this non-specific cytotoxicity, anti-cancer agents not only kill or destroy cancer cells but also destroy rapid proliferative tissues such as bone marrow, lymphatic tissue, epithelial cells of oral cavity and stomach, skin, epithelium of genital glands, etc. Furthermore, when anti-cancer agents are repetitively administered, they can cause many disorders of the organs and tissues, immunodepression, teratogenicity, carcinogenicity, and the like.
Since cancer cells are difficult to destroy by means of one chemotherapeutic agent due to the heterogeneity of human malignant tumors and drug resistance, it is preferable to inhibit the proliferation of cancer cells at all stages by combined therapy of two or more chemotherapeutic agents, each of which affects a different stage in cell proliferation. Accordingly, many attempts have been made to effectively inhibit tumor proliferation, and at the same time to reduce the harmful side effects by such combined therapy.
In this aspect, the present inventors have performed extensive experimental studies using a number of compounds. Pharmacological and pathological examinations allowed us to reveal that acridine derivatives and guanosine compounds are effective against tumor growth. We found that either acridine derivatives or guanosine compounds have extremely low anti-cancer activity when used alone, whereas the two agents in combination exhibit an excellent anti-cancer effect. Thus, we have completed the present invention relating to the composition containing acridine derivatives and guanosine compounds, which acts against cancer.
Accordingly, it is an object of the present invention to provide an anti-cancer composition containing an acridine derivative and a guanosine compound.
The second object of the present invention is to provide an anti-cancer composition containing acriflavine neutral and guanosine hydrate as active ingredients.
The third object of the present invention is to provide an anti-cancer composition containing an acridine derivative and a guanosine compound in the weight ratio of 1:0.1-5.0, preferably 1:0.3-3.0 and more preferably 1:0.5-1.5.
The foregoing has outlined some of the more pertinent objects of the present invention. These objects should be construed to be merely illustrative of some of the more pertinent features ana applications of the invention. Other many beneficial results can be obtained by applying the disclosed invention in a different manner or modifying the invention within the scope of the disclosure. Accordingly, other objects and a more thorough understanding of the invention may be had by referring to the disclosure of invention and the accompanying drawings, in addition to the scope of the invention by the claims.